The long-range goal of the proposed research is to understand the enzymatic mechanisms of deoxynucleoside triphosphate polymerization. Specific emphasis is placed on the characterization and labeling of the active site responsible for the substrate binding using pyridoxal phosphate (PyP) as an active site specific probe. Simultaneously, investigations have been initiated to define the template binding site as well as the location of the intrinsic zinc molecule and its precise role in the process of polymerization.